Murraya koenigii leaves contain mahanimbine, a carbazole alkaloid, reported with improving cholinergic neuronal transmission and reducing neuroinflammation in the CNS. The current research investigated the effects of mahanimbine on age-related memory deficits, oxidative stress, cholinergic dysfunction, amyloid formation, and neuroinflammation in aged mice (16 months old). Mahanimbine was administered (1 and 2 mg/kg, p.o.) daily to groups of aged mice for 30 days. The Morris water maze (MWM) task was performed to study spatial learning (escape latency (EL) and swimming distance (SD)) and memory (probe test). The levels of malondialdehyde (MDA), glutathione (GSH), acetylcholine (ACh), acetylcholinesterase (AChE), beta-amyloid (Abeta(1-40) and Abeta(1-42)), beta-secretase (BACE-1), as well as neuroinflammation markers (total cyclooxygenase (COX) and COX-2 expression), were measured from the isolated brain. Mahanimbine reduced the EL time and SD in the MWM test. From the probe trial, the mahanimbine-treated group spent more time in the targeted quadrant related to the age-matched control, which indicated the enhancement of memory retention. From the biochemical tests, the treatment decreased MDA, AChE, Abeta(1-40), and Abeta(1-42), BACE-1, total COX activity, and COX-2 expression. It also raised the brain GSH and ACh levels in aged mice compared to age-matched control. These results have supported the reversal of memory dysfunctions by mahanimbine in aged mice and hypothesized that it could be a potential target to treat age-related neurodegenerative disease.
Title: Acetylcholinesterase inhibitory potential of a carbazole alkaloid, mahanimbine, from Murraya koenigii Kumar NS, Mukherjee PK, Bhadra S, Saha BP, Pal BC Ref: Phytother Res, 24:629, 2010 : PubMed
In the search for acetylcholinesterase (AChE) inhibitors from Indian medicinal plants, via bioassay-guided isolation, a carbazole alkaloid, mahanimbine [3, 5-dimethyl-3-(4- methylpent-3-enyl)-11H-pyrano [5, 6-a] carbazole], was isolated from the petroleum ether extract of the leaves of Murraya koenigii. Inhibition of AChE was evaluated based on Ellman's method using 96-well microplate readers. Mahanimbine inhibited AChE activity in a dose-dependent manner with an IC(50) value of 0.03 +/- 0.09 mg/mL, while galantamine was used as a standard. The AChE inhibitory activity of this carbazole alkaloid has not been reported so far, and this study is the first to reveal this activity in carbazole alkaloid mahanimbine, isolated from Murraya koenigii.
Title: Pancreatic lipase inhibitory alkaloids of Murraya koenigii leaves Birari R, Roy SK, Singh A, Bhutani KK Ref: Nat Prod Commun, 4:1089, 2009 : PubMed
In the continuing search for newer pancreatic lipase inhibitors from plants, a total of 63 extracts from 21 different plants were screened to study their pancreatic lipase (PL) inhibitory activity in vitro. All three extracts (DCM, EtOAc and MeOH) of Murraya koenigii (L.) Spreng leaves (Rutaceae) exhibited antilipase activity greater than 80%. Further, bioactivity guided fractionation of the EtOAc extract led to the isolation of four alkaloids, namely mahanimbin, koenimbin, koenigicine and clausazoline-K, with IC50 values of 17.9 microM, 168.6 microM, 428.6 microM and <500 microM, respectively. This study reports for the first time the PL inhibitory potential of carbazole alkaloids from plants.
